Long-Term Data Show Significant Improvement in Survival With Ipilimumab in Melanoma

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Nearly twice as many patients with metastatic melanoma who received a combination of ipilimumab and dacarbazine were alive after four years, suggesting that ipilimumab has long-term survival benefits.

Nearly twice as many patients with metastatic melanoma who received a combination of ipilimumab (Yervoy) and dacarbazine were alive after four years compared with patients who received dacarbazine alone, suggesting that ipilimumab has long-term survival benefits and that the combination could serve as an effective treatment regimen.

The results of the long-term follow-up were presented at the European Society for Medical Oncology (ESMO) 2012 Congress in Vienna, Austria.

Ipilimumab, which is administered intravenously, is a monoclonal antibody that blocks the cytotoxic T-lymphocyte antigen (CTLA-4) molecule. CTLA-4 is implicated in suppressing antitumor immune responses. Dacarbazine is a triazene derivative with antineoplastic activity. Both drugs are approved to treat metastatic melanoma.

The follow-up was part of the CA184-024 trial, a phase III double-blind study in which patients with metastatic melanoma who were treatment-naïve were randomized to receive either ipilimumab 10 mg/kg plus dacarbazine 850 mg/m² (n=250) or a placebo plus dacarbazine 850 mg/m² (n=252) given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Patients who achieved stable disease or better received either ipilimumab or a placebo every 12 weeks as maintenance therapy.¹

Patients in the ipilimumab arm of the study had an overall survival rate of 19.0% after 4 years (95% confidence interval [CI], 14.2—24.2) compared with 9.6% among patients in the control arm (95% CI, 6.1–13.5). The median overall survival in the ipilimumab arm was 11.2 months (95% CI, 9.4–13.6) compared with 9.1 months in the control arm (95% CI, 7.8–10.5). The study includes survival data collected through April 2012.

In a statement, manufacturer Bristol-Myers Squibb noted that the dosage of ipilimumab in this study differs from the approved 3 mg/kg dosage approved by the FDA. However, the company stated that a phase III clinical trial comparing the two dose levels is being conducted. Additionally, the combination of ipilimumab and dacarbazine is not yet a FDA-approved regimen.

In another study presented at the ESMO Congress, five-year overall survival rates for three different completed phase II trials of ipilimumab were reported. The three studies included in the analysis were CA184-008, a single-arm study of the 10 mg/kg dose of ipilimumab in previously treated patients; CA184-022, a dose-ranging study of ipilimumab at 0.3, 3, or 10 mg/kg in previously treated patients; and CA184-007, a study of ipilimumab at 10 mg/kg with or without prophylactic budesonide in treatment-naïve and previously treated patients.²

The five-year overall survival rates among all three studies were 12% to 28% in previously treated patients and 38% to 50% in treatment-naïve patients. Across the studies, the researchers found that five-year overall survival rates were similar to those observed at four years, suggesting that certain populations who receive certain dosages of ipilimumab are likely to achieve a significant survival benefit with ipilimumab as a monotherapy.

“Metastatic melanoma is one of the most aggressive forms of cancer with a historical five-year survival rate of less than ten percent in patients with distant metastasis. Results from these investigational studies showed a prolonged survival benefit with Yervoy at four and five years for some patients,” said Celeste Lebbe, MD, professor of Dermatology at Hôpital Saint-Louis in Paris, France and lead author of the five-year survival study in a statement. “These results add to the growing body of long-term survival data seen in some patients treated with Yervoy and further our understanding of the potential of this immunotherapy in the treatment of metastatic melanoma.”

Maio M, Bondarenko I, Robert C, et al. Four-year survival update for metastatic melanoma (mm) patients (pts) treated with ipilimumab (ipi) + dacarbazine (dtic) on phase 3 study CA184-024. Presented at: 37^th European Society of Medical Oncology 2012 Congress; September 28—October 2, 2012; Vienna, Austria. Abstract 1127.
Lebbe C, Weber JS, Maio M, et al. Five-year survival rates for patients (pts) with metastatic melanoma (mm) treated with ipilimumab (ipi) in phase II trials. Presented at: 37^th European Society of Medical Oncology 2012 Congress; September 28—October 2, 2012; Vienna, Austria. Abstract 1116.

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